Tosi M F, Hamedani A, Brosovich J, Alpert S E
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH 44106.
J Immunol. 1994 Feb 15;152(4):1935-42.
Inhalant exposure to ozone can cause diffuse airway epithelial injury that is associated with an inflammatory response, including the influx of neutrophils into lung and airway tissue. We have previously documented enhanced adhesiveness by neutrophils for human airway epithelial cells in in vitro models of diseases associated with airway inflammation and have suggested that this enhanced adhesion may contribute to neutrophil-mediated airway injury. When primary human tracheal epithelial cell (TEC) monolayers were exposed to ozone at 2.0 ppm for 30 min or 0.5 ppm for 2 h, the percentage of PMN adhering to these cells increased from < 5% to a maximum of approximately 75% by 18 to 24 h after the ozone exposure. No change was observed within the first 2 h after ozone exposure, but there was a statistically significant increase in PMN adhesion by 8 h after exposure. In contrast to previous studies with cytokine exposure or respiratory virus infection of TEC, the increased adhesion after ozone exposure was not associated with an increase in epithelial expression of ICAM-1. Consistent with the lack of induction of ICAM-1 by ozone exposure was the observation that anti-ICAM-1 mAbs (mAb; R6.5) previously shown to block PMN adhesion to TEC with increased ICAM-1 expression had no effect on PMN adhesion to ozone-exposed TEC. However, mAbs against CD11b or CD18 on PMN blocked PMN adhesion to ozone-exposed TEC by approximately 55 and 80%, respectively. Chemoattractant preactivation of PMN (e.g., with 10 nM FMLP) was necessary to achieve the highest levels of adhesion to ozone-treated TEC, in marked contrast to our earlier studies with PMN adhesion to cytokine-treated or virus-infected TEC in which resting and prestimulated PMN exhibited the same high levels of adhesion. We conclude that exposure of human TEC in vitro to ozone results in markedly increased adhesiveness for neutrophils that is caused by the induction of as yet uncharacterized epithelial cell adhesion molecules other than ICAM-1 that function as counterreceptors for the CD11/CD18 integrins on PMN. Maximal PMN adhesiveness to ozone-exposed TEC in this system requires preactivation of the PMN, e.g., with FMLP, suggesting important differences in the way PMN interact with ozone-treated vs cytokine-treated or virus-infected TEC.
吸入臭氧可导致弥漫性气道上皮损伤，这与炎症反应相关，包括中性粒细胞流入肺和气道组织。我们之前在与气道炎症相关的疾病体外模型中记录到，中性粒细胞对人气道上皮细胞的黏附性增强，并提出这种增强的黏附可能导致中性粒细胞介导的气道损伤。当原代人气管上皮细胞（TEC）单层暴露于2.0 ppm的臭氧中30分钟或0.5 ppm的臭氧中2小时后，在臭氧暴露后18至24小时，黏附于这些细胞的中性粒细胞百分比从<5%增加到最高约75%。在臭氧暴露后的最初2小时内未观察到变化，但在暴露后8小时中性粒细胞黏附出现统计学显著增加。与之前关于细胞因子暴露或呼吸道病毒感染TEC的研究不同，臭氧暴露后黏附增加与ICAM-1上皮表达增加无关。与臭氧暴露未诱导ICAM-1一致的是，观察到先前显示可通过增加ICAM-1表达来阻断中性粒细胞与TEC黏附的抗ICAM-1单克隆抗体（mAb；R6.5）对中性粒细胞与臭氧暴露的TEC黏附没有影响。然而，针对中性粒细胞上CD11b或CD18的单克隆抗体分别使中性粒细胞与臭氧暴露的TEC黏附减少约55%和80%。中性粒细胞的趋化剂预激活（例如用10 nM FMLP）对于实现对臭氧处理的TEC的最高黏附水平是必要的，这与我们早期关于中性粒细胞与细胞因子处理或病毒感染的TEC黏附的研究形成鲜明对比，在早期研究中，静息和预刺激的中性粒细胞表现出相同的高黏附水平。我们得出结论，体外将人TEC暴露于臭氧会导致对中性粒细胞的黏附性显著增加，这是由除ICAM-1之外尚未鉴定的上皮细胞黏附分子的诱导引起的，这些分子作为中性粒细胞上CD11/CD18整合素的反受体发挥作用。在该系统中，中性粒细胞对臭氧暴露的TEC的最大黏附性需要中性粒细胞的预激活，例如用FMLP，这表明中性粒细胞与臭氧处理的TEC相比与细胞因子处理或病毒感染的TEC相互作用的方式存在重要差异。
